CN117100872B - Nano delivery carrier for targeted tumor drug delivery and application thereof - Google Patents
Nano delivery carrier for targeted tumor drug delivery and application thereof Download PDFInfo
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- CN117100872B CN117100872B CN202310693812.8A CN202310693812A CN117100872B CN 117100872 B CN117100872 B CN 117100872B CN 202310693812 A CN202310693812 A CN 202310693812A CN 117100872 B CN117100872 B CN 117100872B
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- 238000012377 drug delivery Methods 0.000 title claims abstract description 19
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- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims abstract description 19
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- LUKBXSAWLPMMSZ-UHFFFAOYSA-N resveratrol Chemical compound C1=CC(O)=CC=C1C=CC1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
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Abstract
The invention belongs to the technical field of targeted tumor drugs, and particularly relates to a targeted tumor drug delivery nano-delivery carrier and application thereof. The preparation method of the nano delivery carrier comprises the following steps: mixing tumor-targeting aptamer NucA and DSPE-PEG2000-NHS with DMF; and then adding triethylamine to adjust the pH to 8-9, and reacting at room temperature to obtain the targeted tumor drug delivery nano-carrier. The antitumor drug based on the nano delivery carrier can accurately target tumors to be killed, for example, the antitumor drug containing resveratrol based on the nano delivery carrier can target and kill ovarian cancer cells without damaging normal tissues.
Description
Technical Field
The invention belongs to the technical field of targeted tumor drugs, and particularly relates to a targeted tumor drug delivery nano-delivery carrier and application thereof.
Background
Cancer is now an important disease that threatens human life and health. The main treatment means of the tumor at present are surgery, chemotherapy and radiotherapy. The patients in middle and late stages lose the opportunity of operation, and although the primary focus can be removed in the operation, the regeneration, the breeding and the reproduction of cancer cells cannot be fundamentally stopped, and the cancer is easy to relapse after the operation. The means currently adopted are surgery combined with drug treatment, and chemotherapy is generally adopted for drug treatment. Although the chemotherapy can kill cancer cells, a large number of normal tissue cells are damaged at the same time, and the toxic and side effects are obvious, wherein the toxic and side effects comprise debilitation of organism, inappetence, alopecia, inhibition of hematopoiesis, injury of liver, kidney and ovary functions, induction of gastrointestinal reaction, bone marrow suppression, liver, kidney, heart function damage and the like.
The targeting drug refers to a drug or a preparation thereof which is provided with targeting ability, and aims to target a specific lesion site with the drug or a carrier thereof and accumulate or release an active ingredient at the target site. The targeted drug is used in the treatment of cancer, and can reduce or even not damage the body tissues except tumors.
Therefore, it is of great importance to develop a carrier or drug that can be administered targeted to tumors.
Disclosure of Invention
Aiming at the problems, the invention aims to provide a nano delivery carrier capable of targeting tumor drug delivery and application thereof, wherein the nano delivery carrier is formed by connecting a nucleic acid aptamer specifically targeting tumor with DSPE-PEG 2000-NHS; based on the nano delivery carrier for targeted tumor drug delivery, a solvent displacement method can be used, and NHS is replaced by an antitumor active ingredient to prepare the targeted drug for tumor drug delivery.
In order to achieve the above purpose, the present invention may adopt the following technical scheme:
In one aspect, the invention provides a tumor-targeted drug delivery nano delivery vehicle, the preparation method of which comprises the following steps: mixing tumor-targeting aptamer NucA and DSPE-PEG2000-NHS with DMF; and then adding triethylamine to adjust the pH to 8-9, and reacting at room temperature to obtain the nano delivery carrier for targeting tumor drug delivery.
In another aspect, the present invention provides an antitumor drug for targeted drug delivery, which comprises: mixing SPI0 nano particles wrapped by oleic acid, an anti-tumor active ingredient, the targeted tumor drug delivery nano delivery carrier and chloroform to obtain a mixed solution; then gradually adding glycol into the mixed solution under an ultrasonic environment; removing chloroform, adding water, and removing ethylene glycol; then ultrasonic, centrifugating, removing sediment to obtain the targeted anti-tumor drug.
In another aspect, the present invention provides a formulation for treating a tumor comprising an antitumor drug as described above for targeted delivery; and a pharmaceutically acceptable carrier.
The beneficial effects of the invention at least comprise: the antitumor drug based on the nano delivery carrier for targeting tumor administration provided by the invention can be used for preparing the antitumor drug for targeting tumors to be killed, for example, the antitumor drug containing resveratrol based on the nano delivery carrier can be used for targeting and killing ovarian cancer cells without damaging normal tissues.
Drawings
FIG. 1 is a two-position structure diagram of resveratrol;
FIG. 2 is a transmission electron microscope image of PEG-SPIO nanoparticles prepared in the examples;
figure 3 is a transmission electron microscope image of PEG-SPIO-RVT nanoparticles prepared in the examples;
FIG. 4 is a graph showing the results of the hydrated particle size detection of PEG-SPIO and PEG-SPIO-RVT nanoparticles prepared in the examples;
FIG. 5 is a graph of zeta potential analysis of the surface of PEG-SPIO and PEG-SPIO-RVT nanoparticles prepared in the examples;
FIG. 6 is an ultraviolet/visible absorption spectrum of PEG-SPIO and PEG-SPIO-RVT nanoparticles prepared in the examples;
Figure 7 is an in vitro magnetic resonance imaging diagram of PEG-SPIO and PEG-SPIO-RVT nanoparticles prepared in examples with different concentrations of iron ions;
FIG. 8 is a frequency chart of in vitro magnetic resonance imaging of PEG-SPIO and PEG-SPIO-RVT nanoparticles prepared in accordance with the examples with different concentrations of ferric ions;
figure 9 is a graph of the cell viability assay of RVTs;
FIG. 10 is a graph of the cell viability assay of PEG-SPIO;
Figure 11 is a graph of cell viability assay for RVT-entrapped PEG-SPIO-RVT.
Detailed Description
The examples are presented for better illustration of the invention, but the invention is not limited to the examples. Those skilled in the art will appreciate that various modifications and adaptations of the embodiments described above are possible in light of the above teachings and are intended to be within the scope of the invention.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. Unless the context clearly differs, singular forms of expression include plural forms of expression. As used herein, it is understood that terms such as "comprising," "having," "including," and the like are intended to indicate the presence of features, numbers, operations, materials, or combinations. The terms of the present invention are disclosed in the specification and are not intended to exclude the possibility that one or more other features, numbers, operations, materials or combinations thereof may be present or may be added. As used herein, "/" may be interpreted as "and" or "as appropriate.
The embodiment of the invention provides a tumor-targeted drug delivery nano delivery carrier, and the preparation method comprises the following steps: mixing tumor-targeting aptamer NucA and DSPE-PEG2000-NHS with DMF; and then adding triethylamine to adjust the pH to 8-9, and reacting at room temperature to obtain the nano delivery carrier for targeting tumor drug delivery.
The tumor targeting delivery nanocarrier is a tumor targeting delivery nanocarrier DSPE-PEG2000-NHS-NucA formed by connecting aptamer NucA of specific targeting tumor and DSPE-PEG 2000-NHS. In addition, during the preparation process, whether NucA was successfully linked to DSPE-PEG2000-NHS can be determined by Ultraviolet (UV) spectroscopy and infrared spectroscopic analysis (FTIR).
In some embodiments, the molar ratio of the aptamer NucA to DSPE-PEG2000-NHS may be 1 (2.5-3.5), such as 1:2.8, 1:3, or 1:3.2, wherein preferably 1:3, where the targeted tumor delivery nanovehicle prepared at this molar ratio performs optimally.
In some embodiments, the tumor is ovarian cancer. The tumor may be a tumor known in the art, such as breast cancer, lung cancer, gastric cancer, liver cancer, colorectal cancer, or ovarian cancer. When selecting different tumors, it is necessary to select different nucleic acid aptamers.
In some embodiments, when the tumor is ovarian cancer, the aptamer NucA may preferably be a nucleotide sequence as set forth in SEQ ID NO:1, the sequence is: "5' -GGTGGTGGTGGTTGTGGTGGTGGTGG
-/3 Ammc-r/-3' ". It should be noted that "3ammc7-r" is an amino group-NH 2, and the amino group can be bonded to some groups, such as-COOH and-NHS, and the amino group may be modified, or other groups may be modified, i.e., "3ammc7-r" represents a 3' -hydroxyl end modified amino group.
In some embodiments, the room temperature reaction time may be 24 hours. Of course, the reaction time can be controlled according to specific conditions, so long as the nano delivery carrier can be prepared, for example, the time can be 5 hours, 10 hours, 15 hours, 20 hours or the like.
In some embodiments, when the preparation of the tumor targeted delivery nanocarriers described above is completed, dialysis membrane (molecular weight 3.5 kD) may be used for 24 hours to remove unreacted NucA, DSPE-PEG2000-NHS and other organic solvents.
Another embodiment of the present invention provides an antitumor drug for targeted drug delivery, the preparation method of which comprises: mixing SPI0 nano particles wrapped by oleic acid, an anti-tumor active ingredient, the nano delivery carrier for targeting tumor administration and chloroform to obtain a mixed solution; then gradually adding glycol into the mixed solution under an ultrasonic environment; removing chloroform, adding water, and removing ethylene glycol; then ultrasonic, centrifugating, removing sediment to obtain the targeted anti-tumor drug.
It should be noted that, the preparation method of the targeted anti-tumor drug is to replace the original solution with the solution with gradually increased polarity according to the solvent replacement method to prepare the DSPE-PEG2000-RVT-NucA nano-particles.
In the preparation method of the targeted antitumor drug, terms such as "ultrasound" and "centrifugation" are used in the conventional sense in the art, and no specific meaning exists. Additionally, in some embodiments, the centrifugation conditions may be 5000rpm and the ultrasonic power may be 60W.
In some embodiments, the anti-tumor active ingredient is resveratrol. Specifically, the chemical structure of resveratrol is shown in figure 1.
Resveratrol (3, 4', 5-trihydroxy-trans-stilbene) is a natural anti-tumor effective component extracted from plants, and can inhibit tumor occurrence and development, especially ovarian cancer. The application of novel nano-entrapped resveratrol pharmaceutical dosage forms in ovarian cancer has not been reported based on the diversity of the chemical characteristics of the nano-entrapped resveratrol pharmaceutical dosage forms combined with the ovarian cancer related proteins. On the nano delivery carrier for targeting tumor drug delivery, the trans-isomer of resveratrol is reserved, and the binding specificity and stability of resveratrol and a target point are ensured, so that the anticancer sensitization effect is exerted; by means of molecular imaging, the acquisition of the living organism information of the diagnosis and treatment integration of the ovarian cancer by retaining the physical and chemical properties of the natural medicine is realized through a killing experiment of the ovarian cancer cells.
In some embodiments, the mass ratio of oleic acid coated SPI0 nanoparticles, antitumor active ingredient, and the aforementioned tumor targeted delivery nanovehicle for tumor administration may be (4.5-5.5): (0.5-1.5): (9.5-10.5), such as 4.7:0.8:9.7, 5:1:10, or 5.3:1.3:10.3, etc., with 5:1:10 being preferred.
In some embodiments, the amount of ethylene glycol added may be 3-5 times, such as 4 times, the volume of the mixed solution.
It should also be noted that the oleic acid-coated SPI0 nanoparticles described above may be prepared by methods known in the art. For example, an oleic acid iron complex is prepared by a known method, and then the oleic acid is used for coating to obtain the SPI0 nano particles coated with the oleic acid.
In some embodiments, the method of preparing oleic acid-coated SPI0 nanoparticles comprises: (1) Synthesis of iron oleate Complex: reacting FeCl.6H 2 O with sodium oleate in a mixture of ethanol, distilled water and n-hexane; then collecting the complex of the iron oleate, and washing the complex with distilled water; finally, removing hexane in the iron oleate complex by a rotary evaporator to obtain the iron oleate complex; (2) Synthesis of oleic acid-coated SPI0 nanoparticles: mixing the prepared oleic acid iron complex and oleic acid with 1-octadecene, heating to 110 ℃, and vacuumizing for 30 minutes; then, the reaction was slowly heated to 320 ℃ at a rate of 5 ℃ per minute under argon protection and held for 30 minutes; finally, the reaction was cooled to room temperature, taken out, washed with ethanol, and precipitated in chloroform to obtain oleic acid-coated SPI0 nanoparticles.
Another embodiment of the present invention provides a formulation for treating a tumor, comprising the above-described targeted anti-tumor drug; and a pharmaceutically acceptable carrier. It should be noted that, according to clinical needs, the above targeted antitumor drug can be prepared into different dosage forms by adding pharmaceutically acceptable carriers, for example, injection or oral preparation.
For a better understanding of the present invention, the content of the present invention is further elucidated below in connection with the specific examples, but the content of the present invention is not limited to the examples below.
Example 1 nanomaterial synthesis method
(1) Synthesis of iron oleate complex
FeCl 6H 2 O (2.7 g) and sodium oleate (9.125 g) are reacted in a mixture of ethanol (20 mL), distilled water (15 mL) and n-hexane (35 mL) for 4 hours, 70 ℃; the iron oleate complex is then collected using a separatory funnel and washed with distilled water (50 mL); finally, hexane in the iron oleate complex is removed by a rotary evaporator, and the iron oleate complex is packaged in a round bottom flask and stored under room temperature drying conditions.
(2) Synthesis of oleic acid-coated SPIO nanoparticles (OA-SPIO)
Mixing the iron oleate complex (1.0 g) and oleic acid (0.25 g) prepared in the step (1) with 1-octadecene (5.5 g), heating to 110 ℃ and vacuumizing for 30 minutes; then the reactants were slowly heated to 320 ℃ at a rate of 5 ℃ per minute under argon and held for 30 minutes; finally, the reaction was cooled to room temperature, taken out, washed with ethanol and precipitated in chloroform.
(3) Synthesis of DSPE-PEG2000-NHS-NucA (PEG-NucA)
Adding NucA (aptamer) and DSPE-PEG2000-NHS in a molar ratio of 1:3 into DMF solution, and adding triethylamine to adjust pH to 8.5; the solution was reacted at room temperature for 24 hours and then dialyzed against a dialysis membrane (molecular weight 3.5 kD) for 24 hours to remove unreacted NucA, DSPE-PEG2000-NHS and other organic solvents; ultraviolet (UV) spectroscopy and infrared spectroscopy analysis (FTIR) were used to determine whether NucA was successfully attached to DSPE-PEG 2000-NHS.
(4) Synthesis of DSPE-PEG2000-SPIO-RVT-NucA (PEG-SPIO-RVT-NucA)
According to the solvent replacement method, DSPE-PEG2000-RVT-NucA nano particles are prepared, and the specific preparation process is as follows: the OA-SPIO, RVT (resveratrol) and PEG-NucA prepared in the step (3) are mixed according to the mass ratio of 10:2:20 is added into a round-neck flask containing 0.5mL of chloroform, and is placed into an ultrasonic cleaning instrument for short-term ultrasonic treatment, so that each component can be fully dissolved; then, gradually adding 4 times of ethylene glycol solvent into the mixed solution under an ultrasonic environment; evaporating to remove chloroform by a rotary evaporator, adding a proper amount of deionized water into the solution, and removing glycol solution by multiple centrifugation by an ultrafiltration tube (100 mw); next, the cells were sonicated with a cell sonicator at 60W power for 5 minutes; finally, the solution was centrifuged at 5000rpm to remove the precipitate and to remove large aggregates to give PEG-SPIO-RVT-NucA.
The PEG-SPIO and PEG-SPIO-RVT synthesis methods of the control group are the same as described above.
Example 2 nanomaterial characterization
The PEG-SPIO nanoparticle and the PEG-SPIO-RVT nanoparticle prepared in example 1 were subjected to transmission electron microscopy analysis, respectively, and the results are shown in FIG. 2 and FIG. 3.
The PEG-SPIO nanoparticle and PEG-SPIO-RVT nanoparticle prepared in the above example 1 were subjected to hydration particle size detection, respectively, and the results are shown in FIG. 4;
the PEG-SPIO nanoparticles and PEG-SPIO-RVT nanoparticles prepared in example 1 above were subjected to surface zeta potential analysis, respectively, and the results are shown in fig. 5.
The PEG-SPIO nanoparticle and PEG-SPIO-RVT nanoparticle prepared in example 1 were subjected to ultraviolet/visible light absorption spectroscopy, respectively, and the results are shown in FIG. 6.
The PEG-SPIO nanoparticle and the PEG-SPIO-RVT nanoparticle prepared in the embodiment 1 are respectively subjected to in vitro magnetic resonance imaging analysis under different concentrations, an in vitro magnetic resonance imaging analysis chart is shown in fig. 7, and in vitro magnetic resonance imaging frequencies are shown in fig. 8.
Example 3 cell viability assay
In order to verify whether Resveratrol (RVT) can cause death of tumor cells, SKOV3 cells are treated for 24 hours by using RVT with different concentrations, then the activity of the cells is detected by using a CCK-8 detection reagent, and as a result, as shown in figure 9, the activity of the SKOV3 cells gradually shows a decreasing trend along with the increase of the RVT concentration.
In addition, SKOV3 cells were treated with PEG-SPIO at various concentrations for 24 hours, and their cell viability was examined using CCK-8 detection reagent, as shown in FIG. 10, which did not result in SKOV3 cell death at concentrations as high as 200. Mu.g/mL, indicating that PEG-SPIO had no significant cytotoxicity to cells.
Furthermore, the PEG-SPIO-RVT nanoparticle with the RVT is treated for 24 hours on SKOV3 cells, and the CCK-8 detection reagent is used for detecting the cell viability, so that the result is shown in figure 11, the result is the same as that of the individual RVT, and the cell viability is obviously reduced along with the increase of the concentration of the PEG-SPIO-RVT nanoparticle.
The above results indicate that RVT is a real cause of SKOV3 cell death.
Example 4 ovarian cancer tumor cell killing validation
Experiments on ovarian cancer tumor cells prove that the natural drug targeting delivery system has a killing effect on the ovarian cancer cells, and normal tissues are not damaged.
Finally, it is noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the scope of the claims of the present invention.
Claims (5)
1. The preparation method of the antitumor drug for targeted drug delivery is characterized by comprising the steps of mixing SPI0 nano particles wrapped by oleic acid, antitumor active ingredients, a nano delivery carrier for targeted drug delivery for tumor delivery and chloroform to obtain a mixed solution; then gradually adding glycol into the mixed solution under an ultrasonic environment; removing chloroform, adding water, and removing ethylene glycol; then ultrasonic, centrifuging, removing sediment to obtain the targeted anti-tumor drug;
The antitumor active ingredient is resveratrol;
The tumor-targeted nano delivery carrier is prepared by the following preparation method: mixing tumor-targeting aptamer NucA and DSPE-PEG2000-NHS with DMF; then adding triethylamine to adjust the pH to 8-9, and reacting at room temperature to obtain the nano delivery carrier for targeting tumor drug delivery;
the tumor is ovarian cancer; the nucleic acid aptamer NucA is shown in SEQ ID NO:1, a sequence shown in seq id no;
the molar ratio of the nucleic acid aptamer NucA to DSPE-PEG2000-NHS is 1 (2.5-3.5).
2. The targeted anti-tumor drug according to claim 1, wherein the mass ratio of the oleic acid-coated SPI0 nanoparticle, the anti-tumor active ingredient, and the targeted tumor delivery nanovehicle is (4.5-5.5): (0.5-1.5): (9.5-10.5).
3. The targeted antitumor drug of claim 1, wherein the amount of ethylene glycol added is 3-5 times the volume of the mixed solution.
4. A formulation for the treatment of tumors, characterized in that it comprises an antitumor drug according to any one of claims 1 to 3, targeted for administration; and a pharmaceutically acceptable carrier.
5. The formulation for treating tumors of claim 4, which is characterized in that the pharmaceutically acceptable carrier is suitable for injection or oral administration.
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"Aptamer-Modified Zinc Ferrite Nanoparticles for Autophagy-Mediated Chemotherapy and MR Imaging of Ovarian Cancer";Zhu, JL 等;《ACS APPLIED NANO MATERIALS》;20240104;第7卷(第1期);第1055-1066页 * |
"Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine-Rich Quadruplex Nucleotide–Lipid Derivative for Treatment of Resistant Breast Cancer";Xueqi Li 等;《Small》;20210131;第17卷;文献编号2007391第1-11页 * |
"多功能纳米探针IR820@PEG-SPIO在微小肝癌诊断及腹腔镜辅助光热治疗的研究";李乔林;《中国博士学位论文全文数据库 医药卫生科技辑》;20210615;第E072-189页 * |
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